TY - JOUR
T1 - Chronic aminoguanidine attenuates renal dysfunction and injury in aging rats
AU - Reckelhoff, Jane F.
AU - Hennington, Bettye Sue
AU - Kanji, Vijaya
AU - Racusen, Lorraine C.
AU - Schmidt, Ann Marie
AU - Yan, Shi Du
AU - Morrow, Jason
AU - Roberts, L. Jackson
AU - Salahudeen, Abdulla K.
N1 - Funding Information:
These studies were supported by grants HL51971 and GM42056 from the National Institutes of Health and the American Heart Association, Mississippi Affiliate.
PY - 1999/5
Y1 - 1999/5
N2 - We have previously shown that aging is associated with increased lipid peroxidation, reductions in renal function, and increased glomerular sclerosis. The mechanism(s) responsible for these age-related changes are not clear. The purpose of the present studies was to determine if there was an increase in inducible nitric oxide synthase (iNOS) with aging, and if so, whether inhibition of iNOS would prevent aging injury by preventing free radical-mediated lipid peroxidation, iNOS protein expression in the kidney increased by approximately 90% by 24 months. Inhibition of iNOS by aminoguanidine (0.1% in drinking water) for 9 months, beginning at 13 months of age, reduced blood pressure, improved glomerular filtration rate by 70%, and renal plasma flow by 40%, whereas glomerular sclerosis was considerably reduced. Renal F2-isoprostanes and malondialdehyde levels, markers of oxidative stress and lipid peroxidation, were not reduced by aminoguanidine. Aminoguanidine also did not attenuate immunostaining for advanced glycosylation end products (AGE) in the kidneys. These findings suggest that aminoguanidine attenuates aging renal dysfunction by inhibiting a pathophysiologic function of iNOS that is independent of free radical- mediated lipid peroxidation or significant effects on AGE deposition.
AB - We have previously shown that aging is associated with increased lipid peroxidation, reductions in renal function, and increased glomerular sclerosis. The mechanism(s) responsible for these age-related changes are not clear. The purpose of the present studies was to determine if there was an increase in inducible nitric oxide synthase (iNOS) with aging, and if so, whether inhibition of iNOS would prevent aging injury by preventing free radical-mediated lipid peroxidation, iNOS protein expression in the kidney increased by approximately 90% by 24 months. Inhibition of iNOS by aminoguanidine (0.1% in drinking water) for 9 months, beginning at 13 months of age, reduced blood pressure, improved glomerular filtration rate by 70%, and renal plasma flow by 40%, whereas glomerular sclerosis was considerably reduced. Renal F2-isoprostanes and malondialdehyde levels, markers of oxidative stress and lipid peroxidation, were not reduced by aminoguanidine. Aminoguanidine also did not attenuate immunostaining for advanced glycosylation end products (AGE) in the kidneys. These findings suggest that aminoguanidine attenuates aging renal dysfunction by inhibiting a pathophysiologic function of iNOS that is independent of free radical- mediated lipid peroxidation or significant effects on AGE deposition.
KW - Advanced glycosylation end products
KW - F2-isoprostanes
KW - Free radicals
KW - Glomerular filtration rate
KW - Lipid peroxidation
KW - Renal plasma flow
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U2 - 10.1016/S0895-7061(98)00264-7
DO - 10.1016/S0895-7061(98)00264-7
M3 - Article
C2 - 10342787
AN - SCOPUS:0033003723
SN - 0895-7061
VL - 12
SP - 492
EP - 498
JO - American Journal of Hypertension
JF - American Journal of Hypertension
IS - 5
ER -